DESCRIPTION: Following completion of reverse transcription, the HIV cDNA becomes integrated into a host chromosome. For this to take place, the HIV "preintegration complex" (PIC) must be transported to the location of the host chromosomes. For the case of multiplication of non-dividing cells, a characteristic of HIV, the PIC must pass through the host nuclear membrane to achieve integration. Dr. Bukrinsky has made a number of contribution in studies of subcellular sorting of PICs, and proposed to continue his studies in this renewal. Work will focus on the viral-encoded protein vpr. In a nuclear localization sequence (NLS) in MA protein and the vpr protein contribute karyophillic signals to the PIC. Extensive work by others has elucidated several of the proteins involved in nuclear localization, including karyopherins, proteins that function in part by binding NLS sequences. In this renewal, Dr. Bukrinsky proposes to: 1) characterize the Vpr-karyopherin alpha interaction; 2) investigate the effects of Vpr on interactions of karyopherins with MA and other NLS-containing proteins; 3) demonstrate the effect of Vpr on the process of nuclear import; and 4) determine the role of Vpr and Vpx in HIV-2/SIV nuclear import. The investigator has published extensively in this area and is familiar with many of the methods necessary to carry out the study.